Colorectal cancer is the third-leading cause of cancer death in the United States. This is troubling given that screening rates are marked by a pronounced disparity, with Latinos who have been in the United States for fewer than 10 years and the uninsured having the lowest rates. These individuals generally receive care at one of over 1,200 federally qualified health centers (FQHCs) that serve over 21 million persons nationwide. While colorectal cancer screening rates among FQHC patients are a cause for great concern, studies have demonstrated success for improving screening rates. Programs that mail fecal immunochemical testing (FIT) kits with pictograph instructions to eligible patients report higher screening rates. While new technologies, such as automated phone calls and text messages, have been explored to remind patients to complete screening, little is known about their effectiveness in diverse populations. Moreover, such programs often adopt a one-size fits all approach and their effectiveness has not been tested among subgroups least likely to be screened. To address these issues, we will work with the advisory board assembled for our successful STOP CRC project and additional community stakeholders to adapt and spread a direct-mail FIT and reminder program (PROMPT) in two phases. In Phase I, we will design and evaluate a randomized controlled trial to test systems-based, automated and non-automated strategies to increase colorectal cancer screening in an FQHC with diverse patient populations. In Phase II, we will assess the spread of the program to 11 clinics (estimated age-eligible patient population ~ 22,000). The proposed study's design and evaluation will be guided by the RE-AIM framework using intervention mapping and will involve low-income and ethnically diverse patients who are served by Yakima Valley Farmworkers Clinic. PROMPT will be the first trial to sequentially test the effectiveness of reminders to a direct-mail colorectal cancer screening program, then spread the selected best practice to additional clinics within the FQHC network. PROMPT will apply novel and locally develop strategies to engage stakeholders in adapting the intervention, defining the intervention components, and selecting a best practice for spread. If the trial succeeds, it will have broad-scale implementation potential for a similar program to decrease cancer screening disparities.